Microneedling with a Novel, n-3-PUFA-Rich Formulation Accelerates Inflammation Resolution to Improve Skin Recovery Outcomes in Adults with Healthy Skin.

INTRODUCTION: Microneedling is a cosmetic procedure that leverages the skin's natural ability to heal in order to promote collagen formation and skin rejuvenation. To provide improved results, the technique can be combined with topical formulations. A new formulation of multiple actives, including omega-3 (n-3) polyunsaturated fatty acids (PUFAs), was designed to accelerate the resolution of inflammation and wound healing following micro-injury treatments, while enhancing the visible appearance of procedure results, including erythema, luminosity and skin texture. METHODS: In this randomised, controlled, split-face study, we examined 32 healthy female participants aged 30-70 years for 4 weeks following microneedling treatment with a novel multiple-active-ingredient formulation or conventional microneedling protocol with a hyaluronic acid control serum. Changes in skin condition were assessed by blinded clinical photography and expert evaluation. Measurements were collected at baseline, 1 h, 1 day, 7 days and 28 days post treatment. RESULTS: Significantly greater improvements in expert-assessed erythema, luminosity and skin texture were reported following application of the novel multiple-active-ingredient formulation than the hyaluronic acid control serum. This was confirmed by representative VISIA®-CR imaging. CONCLUSION: These data provide new evidence for the role of a novel multiple-active-ingredient formulation for improving skin outcomes up to 28 days following microneedling in adults with healthy skin when compared with a hyaluronic acid serum. The n-3 PUFA content of this formulation may drive accelerated inflammation resolution and wound healing alongside the complementary action of the other active ingredients, leading to the observed improvements in erythema, luminosity and skin texture.

A community-wide approach to reducing risky drinking cultures in young people in rural Australia.

OBJECTIVE: This study evaluated the impact of a multi-faceted, harm minimisation program addressing youth alcohol change and risky drinking behaviours in rural Australia. The role and influence of a multi-tiered community approach to changing alcohol cultures is examined. SETTING: An alcohol culture change project for young people (12-18 years) was implemented in rural Victoria. It was informed by the Alcohol Cultures Framework, comprising community-wide events and youth-focused activities, co-designed with young people. The approach aimed at maximising engagement and reducing alcohol-related harm by targeting the shared activities and drinking practices of young people, parents and the community. PARTICIPANTS: Participants (n = 446) provided feedback specific to three key program activities for promoting alcohol change. DESIGN: Mixed methods: Feedback sheets were collected, and interviews and focus groups were conducted with program participants. RESULTS: Participants indicated that the program had informed their understanding of the way people in their region drink, and the social norms and practices around alcohol that encourage risky drinking. It influenced their short- and medium-term reactions, learnings and activities relating to alcohol consumption. The impact of the program was greatest in adults than young people although reflective learning and some behaviour change were evident across all age groups and community clusters. CONCLUSION: Community-wide health promotion events offer participants a deeper understanding of the ways in which dominant alcohol cultures inform the practices and activities of young people within a broader community context. Ensuring health promotion programs within a whole-of-community approach are established longer term, is recommended.

Muscle wasting in cancer: opportunities and challenges for exercise in clinical cancer trials.

Background: Low muscle in cancer is associated with an increase in treatment-related toxicities and is a predictor of cancer-related and all-cause mortality. The mechanisms of cancer-related muscle loss are multifactorial, including anorexia, hypogonadism, anaemia, inflammation, malnutrition, and aberrations in skeletal muscle protein turnover and metabolism. Methods: In this narrative review, we summarise relevant literature to (i) review the factors influencing skeletal muscle mass regulation, (ii) provide an overview of how cancer/treatments negatively impact these, (iii) review factors beyond muscle signalling that can impact the ability to participate in and respond to an exercise intervention to counteract muscle loss in cancer, and (iv) provide perspectives on critical areas of future research. Results: Despite the well-known benefits of exercise, there remains a paucity of clinical evidence supporting the impact of exercise in cancer-related muscle loss. There are numerous challenges to reversing muscle loss with exercise in clinical cancer settings, ranging from the impact of cancer/treatments on the molecular regulation of muscle mass, to clinical challenges in responsiveness to an exercise intervention. For example, tumour-related/treatment-related factors (e.g. nausea, pain, anaemia, and neutropenia), presence of comorbidities (e.g. diabetes, arthritis, and chronic obstructive pulmonary disease), injuries, disease progression and bone metastases, concomitant medications (e.g., metformin), can negatively affect an individual's ability to exercise safely and limit subsequent adaptation. Conclusions: This review identifies numerous gaps and oppportunities in the area of low muscle and muscle loss in cancer. Collaborative efforts between preclinical and clinical researchers are imperative to both understanding the mechanisms of atrophy, and develop appropriate therapeutic interventions.

In-hospital respiratory viral infections for patients with established BPD in the SARS-CoV-2 era.

OBJECTIVE: Our objective was to test the hypothesis that in-hospital respiratory viral infections (RVI) would be significantly lower in a cohort of patients with established bronchopulmonary dysplasia (BPD) exposed to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection prevention protocol when compared to historical controls. STUDY DESIGN: On April 1, 2020, we implemented a universal infection prevention protocol to minimize the risk of nosocomial SARS-CoV-2 transmission in a dedicated BPD intensive care unit. We performed a retrospective cohort study and included patients with established BPD, as defined by the 2019 Neonatal Research Network criteria, admitted to our center who underwent real-time polymerase-chain-reaction RVI testing between January 1, 2015 and March 31, 2021. We excluded patients readmitted from home. We compared the proportion of positive tests to the number of tests performed and the distribution of viral respiratory pathogens in the pre- and post-SARS-CoV-2 eras. RESULTS: Among 176 patients included in the study, 663 RVI tests were performed and 172 (26%) tests were positive. The median number of tests performed, measured in tests per patient per month, in the SARS-CoV-2 era was not significantly different compared to the pre-SARS-CoV-2 era (0.45 vs. 0.34 tests per patient per month, p = .07). The proportion of positive RVI tests was significantly lower in the SARS-CoV-2 era when compared to the pre-SARS-CoV-2 era (0.06 vs. 0.30, p < .0001). No patients tested positive for SARS-CoV-2 in the SARS-CoV-2 era. CONCLUSIONS: Infection prevention measures developed in response to the SARS-CoV-2 pandemic may reduce the risk of RVIs in hospitalized patients with established BPD.

Characterization, bio-uptake and toxicity of polymer-coated silver nanoparticles and their interaction with human peripheral blood mononuclear cells.

Silver nanoparticles (AgNPs) are widely used in medical applications due to their antibacterial and antiviral properties. Despite the extensive study of AgNPs, their toxicity and their effect on human health is poorly understood, as a result of issues such as poor control of NP properties and lack of proper characterization. The aim of this study was to investigate the combined characterization, bio-uptake, and toxicity of well-characterized polyvinylpyrrolidone (PVP)-coated AgNPs in exposure media during exposure time using primary human cells (peripheral blood mononuclear cells (PBMCs)). AgNPs were synthesized in-house and characterized using a multimethod approach. Results indicated the transformation of NPs in RPMI medium with a change in size and polydispersity over 24 h of exposure due to dissolution and reprecipitation. No aggregation of NPs was observed in the RPMI medium over the exposure time (24 h). A dose-dependent relationship between PBMC uptake and Ag concentration was detected for both AgNP and AgNO3 treatment. There was approximately a two-fold increase in cellular Ag uptake in the AgNO3 vs the NP treatment. Cytotoxicity, using LDH and MTS assays and based on exposure concentrations was not significantly different when comparing NPs and Ag ions. Based on differential uptake, AgNPs were more toxic after normalizing toxicity to the amount of cellular Ag uptake. Our data highlights the importance of correct synthesis, characterization, and study of transformations to obtain a better understanding of NP uptake and toxicity. Statistical analysis indicated that there might be an individual variability in response to NPs, although more research is required.

High-fat diet-fed ovariectomized mice are susceptible to accelerated subcutaneous tumor growth potentially through adipose tissue inflammation, local insulin-like growth factor release, and tumor associated macrophages.

BACKGROUND: The association between obesity and colorectal cancer (CRC) risk has been well established. This relationship appears to be more significant in men than in women, which may be attributable to sex hormones. However, controlled animal studies to substantiate these claims and the mechanisms involved are lacking. MATERIALS AND METHODS: MC38 murine colon adenocarcinoma cells were injected subcutaneously into high-fat diet (HFD) fed male, female and ovariectomized (OVX) female C57BL/6 mice. RESULTS: HFD increased tumor growth (main effect) that was consistent with metabolic perturbations (P < 0.01). HFD OVX mice exhibited the most significant tumor growth compared to HFD male and female mice (p < 0.05) and this was associated with increased subcutaneous adipose tissue (p < 0.05). Further, the subcutaneous adipose tissue depots within HFD OVX mice exhibited more severe macrophage associated inflammation compared to female (P < 0.01), but not male mice. Conditioned media from subcutaneous adipose tissue of HFD OVX contained higher IGF-1 levels compared to male (P < 0.01), but not female mice. Finally, HFD OVX mice had increased M2-like gene expression in their tumor-associated macrophages (TAMs) compared to female mice (P < 0.01). CONCLUSIONS: This work provides evidences suggesting adiposity, adipose specific IGF-1, macrophage associated adipose inflammation, and TAMs as potential mechanisms driving obesity-enhanced CRC in females lacking ovarian hormones.

Talectomy by Medial Surgical Approach for Congenital Vertical Talus in Arthrogryposis Multiplex Congenita.

Arthrogryposis multiplex congenita involves stiff contracture of joints and weak atrophic muscles presenting at birth. The two most common forms are amyoplasia and distal arthrogryposis. Amyoplasia affects all 4 extremities: internally rotated shoulders, extended fixed elbows, flexed fixed wrists, extended fixed knees, clubfeet, and decreased muscle volume. Distal arthrogryposis is a group of syndromes with a genetic basis. The distal joints are contracted. Clubfeet and congenital vertical talus are the most common foot deformities. A 10-year-old boy presented with distal arthrogryposis with bilateral congenital tali. He reported having deformed and painful feet and difficulty wearing shoes. His rocker-bottom foot deformities caused him to walk with a heel to heel gait. He also had stiff extended knees. His previous foot surgeries included failed open reduction and pin fixation of the talonavicular joints with Achilles tendon lengthening and capsulotomies. The boy underwent bilateral talectomies and releases of contracted joint capsules and lengthening of multiple extrinsic tendons through separate incisions. The talectomy of each foot was performed via a novel medial surgical approach. At 2-year follow-up, he had normal-appearing plantar grade feet. He had a painless gait, could ambulate independently, and was considered to have an excellent result. This is the first detailed report of performing a talectomy via a medial approach for bilateral congenital tali in a patient with arthrogryposis multiplex congenita. [Orthopedics. 2020; 43(6):e623-e626.].

The impact of a randomized dietary and physical activity intervention on chronic inflammation among obese African-American women.

Lifestyle interventions may reduce inflammation and lower breast cancer (BrCa) risk. This randomized trial assessed the impact of the Sistas Inspiring Sistas Through Activity and Support (SISTAS) study on plasma C-reactive protein (CRP), interleukin-6 (IL-6) and Dietary Inflammatory Index (DII). This unblinded, dietary and physical activity trial was implemented in 337 obese (body mass index [BMI] ≥30 kg/m2) African American (AA) women recruited between 2011 and 2015 in South Carolina through a community-based participatory approach with measurements at baseline, 3 months, and 12 months. Participants were randomized into either intervention (n = 176) or wait-list control group (n = 161). Linear mixed-effect models were used for analyses of CRP and IL-6. Baseline CRP was significantly higher in those with greater obesity, body fat percentage, and waist circumference (all p <.01). No difference was observed between groups for CRP or IL-6 at 3 or 12 months; however, improvements in diet were observed in the intervention group compared to the control group (p = .02) at 3 months but were not sustained at 12 months. Although the intervention was not successful at reducing levels of CRP or IL-6, a significant decrease was observed in DII score for the intervention group, indicating short-term positive dietary change.

The Nutritious Eating with Soul (NEW Soul) Study: Study design and methods of a two-year randomized trial comparing culturally adapted soul food vegan vs. omnivorous diets among African American adults at risk for heart disease.

BACKGROUND: Previous research has found that African American (AA) vegetarians/vegans have a significantly lower body mass index and risk of hypertension compared to omnivores. OBJECTIVES: The Nutritious Eating with Soul (NEW Soul) study partnered with local soul food restaurants/chefs to deliver two behavioral nutrition interventions to AA adults. NEW Soul examines the impact of two different culturally tailored diets (vegan and omnivorous low-fat) on changes in risk factors for cardiovascular disease (CVD). METHODS: AA adults with overweight or obesity are recruited from the community in the Midlands of South Carolina. Eligible participants are randomized to follow one of two different culturally-adapted, soul food diets: a vegan diet emphasizing minimally-processed whole foods from plants or a low-fat omnivorous diet. Participants attend weekly group classes for the first six months, bi-weekly for the next six months, and monthly meetings for the last year. In addition to face-to-face content, participants also have access to private Facebook groups for their diet, podcasts, and online newsletters starting at six months. Primary outcomes include changes in body weight and CVD risk factors (lipids, blood pressure, glucose, and insulin) at 12 months. Secondary outcomes include changes in dietary intake. Participants complete assessments at baseline and at months 6, 12, and 24. CONCLUSIONS: The NEW Soul study is an innovative intervention aimed at improving dietary intake while maintaining traditional AA cultural food choices. Primary outcomes are expected by 2021.

Gut Antibody Deficiency in a Mouse Model of CVID Results in Spontaneous Development of a Gluten-Sensitive Enteropathy.

Primary immunodeficiencies are heritable disorders of immune function. CD19 is a B cell co-receptor important for B cell development, and CD19 deficiency is a known genetic risk factor for a rare form of primary immunodeficiency known as "common variable immunodeficiency" (CVID); an antibody deficiency resulting in low levels of serum IgG and IgA. Enteropathies are commonly observed in CVID patients but the underlying reason for this is undefined. Here, we utilize CD19-/- mice as a model of CVID to test the hypothesis that antibody deficiency negatively impacts gut physiology under steady-state conditions. As anticipated, immune phenotyping experiments demonstrate that CD19-/- mice develop a severe B cell deficiency in gut-associated lymphoid tissues that result in significant reductions to antibody concentrations in the gut lumen. Antibody deficiency was associated with defective anti-commensal IgA responses and the outgrowth of anaerobic bacteria in the gut. Expansion of anaerobic bacteria coincides with the development of a chronic inflammatory condition in the gut of CD19-/- mice that results in an intestinal malabsorption characterized by defects in lipid metabolism and transport. Administration of the antibiotic metronidazole to target anaerobic members of the microbiota rescues mice from disease indicating that intestinal malabsorption is a microbiota-dependent phenomenon. Finally, intestinal malabsorption in CD19-/- mice is a gluten-sensitive enteropathy as exposure to a gluten-free diet also significantly reduces disease severity in CD19-/- mice. Collectively, these results support an effect of antibody deficiency on steady-state gut physiology that compliment emerging data from human studies linking IgA deficiency with non-infectious complications associated with CVID. They also demonstrate that CD19-/- mice are a useful model for studying the role of B cell deficiency and gut dysbiosis on gluten-sensitive enteropathies; a rapidly emerging group of diseases in humans with an unknown etiology.

New Single-stage Double Osteotomy for Late-presenting Infantile Tibia Vara: A Comprehensive Approach.

BACKGROUND: Successful surgical treatment of late-presenting infantile tibia vara (ITV) patient requires the correction of oblique deformities. The purpose of this study was to report on a new comprehensive approach to correct and prevent recurrence of these deformities with a single procedure. METHODS: Medical records of 23 consecutive children (7 to 18 y) with advanced ITV (29 knees) were retrospectively reviewed after a mean of 7.3 years postoperatively (range, 2 to 22 y). Indications for the corrective surgery were any child 7 year or older with a varus mechanical axis angle ≥10 degrees or a varus anatomic axis angle ≥11 degrees and a medial tibial angle (MTA) slope <60 degrees. The deformities were corrected with a dome-shaped osteotomy proximal to the tibial tubercle with a midline vertical extension to the subchondral region of the joint and a lateral hemi-epiphysiodesis. RESULTS: At latest follow-up, means and medians of each tibial radiographic axis measurement improved significantly from preoperative values (P<0.001): mechanical axis angle from 23 degrees to 4 degrees varus, anatomic axis angle from 25 degrees varus to 1 degree valgus, MTA downward slope from 30 to 78 degrees, posterior MTA from 59 to 80 degrees. In total, 79% and 74% had good to excellent results based on radiographic criteria and clinical questionnaire for satisfaction, pain and function, respectively. Two abnormal medial tibial plateau types were described. CONCLUSIONS: This is the first study to use a single-stage double osteotomy performed proximal to the tibial tubercle for the late-presenting ITV for children 7 years of age or older. In addition to the effective correction of the 4 major tibial deformities, a lateral proximal tibial hemi-epiphysiodesis minimizes recurrence of tibia vara. A contralateral proximal tibial epiphysiodesis is recommended for treated skeletally immature patients with unilateral disease. LEVEL OF EVIDENCE: Therapeutic level IV. See instructions for authors for a complete description of levels of evidence.

A randomised controlled trial of the Group Stepping Stones Triple P training programme for parents of children with developmental disabilities.

The central aim of this study was to examine the effectiveness of Group Stepping Stones Triple P (GSSTP) in an Irish context for families of children with both developmental disabilities and internalising and externalising behavioural problems. Parents of 84 children (mean age = 5.73; SD = 2.06) with developmental disabilities and co-occurring behaviour problems attending Irish public health services were randomly assigned to a 9-week GSSTP group or a waiting list control (WLC) group. All parents completed self-report measures before (Time 1) and after (Time 2) the programme and parents in the GSSTP group were assessed at 3- to 5-month follow-up (Time 3). At Time 2, clinical improvement and reliable change rates on the primary dependent variables (summary scales of the Developmental Behaviour Checklist and Strengths and Difficulties Questionnaire) were significantly higher in the GSSTP group than in the WLC group. At Time 2, mean scores of the GSSTP group showed significant, small to medium improvements relative to the WLC group on parent-reported child behaviour problems, parenting skills and confidence, and parental adjustment. Most of these improvements were maintained at 3- to 5-month follow-up. These results indicate that GSSTP is a promising intervention for improving child behaviour and parenting outcomes in a mixed-disability group in an Irish context.

Differential role of CXCR3 in inflammation and colorectal cancer.

Chemokines (CXCR3) and their ligands (CXCL9, CXCL10, and CXCL11) exert exquisite control over T-cell trafficking and are critical for activation, differentiation and effector T cell function. CXCR3 is important for CD4 Th1 cells, CD8 effectors, memory cells, and for the function of natural killer and natural killer T cells. The presence of high cytotoxic CXCR3 ligand expression on CD8 T cells in colorectal cancerous tissue has been well documented in the past. CXCR3 and its ligands are differentially expressed at sites of inflammation and within the tumors. Further, the expression of CXCR3 and its ligands has been correlated with both the presence of effector T cells within tumor tissue and disease-free survival of patients. However, effector T cell infiltration into primary and metastatic tumors is highly variable and, in fact, often absent. Thus, understanding why T cells fail to infiltrate into tumors and determining the way to improve effector T cell entry into tumors would be important advances in efforts to harness the power of the immune system to fight cancer. To this end, the recent exciting discovery that CXCR3 is functionally expressed on regulatory T cells and also induces the differentiation of peripheral CD4 T cells into regulatory T cells, might address the novel clinically relevant question of the therapeutic potential of the CXCR3 system. This is also coupled with the fact that increases in CXCR3 expression also improves effector T cell function. This review describes the differential role of CXCR3 induction on peripheral and tumor microenvironment inflammation. Further, this review, tied with important findings from our laboratory, demonstrates that polyphenols induce CXCR3 expression on regulatory T cells and increases CXCR3 ligands in the tumor microenvironment, which act together to suppress colorectal cancer through a differential mechanism discussed herewith.

Resveratrol protects mice against SEB-induced acute lung injury and mortality by miR-193a modulation that targets TGF-ß signalling.

Staphylococcal enterotoxin B (SEB) is a potent superantigen produced by Staphylococcus aureus that triggers a strong immune response, characterized by cytokine storm, multi-organ failure, and often death. When inhaled, SEB can cause acute lung injury (ALI) and respiratory failure. In this study, we investigated the effect of resveratrol (RES), a phytoallexin, on SEB-driven ALI and mortality in mice. We used a dual-exposure model of SEB in C3H/HeJ mice, which caused 100% mortality within the first 5 days of exposure, and treatment with RES resulted in 100% survival of these mice up to 10 days post-SEB exposure. RES reduced the inflammatory cytokines in the serum and lungs, as well as T cell infiltration into the lungs caused by SEB. Treatment with RES also caused increased production of transforming growth factor-beta (TGF-ß) in the blood and lungs. RES altered the miRNA profile in the immune cells isolated from the lungs. Of these, miR-193a was strongly induced by SEB and was down-regulated by RES treatment. Furthermore, transfection studies and pathway analyses revealed that miR-193a targeted several molecules involved in TGF-ß signalling (TGFß2, TGFßR3) and activation of apoptotic pathways death receptor-6 (DR6). Together, our studies suggest that RES can effectively neutralize SEB-mediated lung injury and mortality through potential regulation of miRNA that promote anti-inflammatory activities.

Oxygen Administration Improves Survival but Worsens Cardiopulmonary Functions in Chlorine-exposed Rats.

Chlorine is a highly reactive gas that can cause significant injury when inhaled. Unfortunately, its use as a chemical weapon has increased in recent years. Massive chlorine inhalation can cause death within 4 hours of exposure. Survivors usually require hospitalization after massive exposure. No countermeasures are available for massive chlorine exposure and supportive-care measures lack controlled trials. In this work, adult rats were exposed to chlorine gas (LD58-67) in a whole-body exposure chamber, and given oxygen (0.8 FiO2) or air (0.21 FiO2) for 6 hours after baseline measurements were obtained. Oxygen saturation, vital signs, respiratory distress and neuromuscular scores, arterial blood gases, and hemodynamic measurements were obtained hourly. Massive chlorine inhalation caused severe acute respiratory failure, hypoxemia, decreased cardiac output, neuromuscular abnormalities (ataxia and hypotonia), and seizures resulting in early death. Oxygen improved survival to 6 hours (87% versus 42%) and prevented observed seizure-related deaths. However, oxygen administration worsened the severity of acute respiratory failure in chlorine-exposed rats compared with controls, with increased respiratory acidosis (pH 6.91 ± 0.04 versus 7.06 ± 0.01 at 2 h) and increased hypercapnia (180.0 ± 19.8 versus 103.2 ± 3.9 mm Hg at 2 h). In addition, oxygen did not improve neuromuscular abnormalities, cardiac output, or respiratory distress associated with chlorine exposure. Massive chlorine inhalation causes severe acute respiratory failure and multiorgan damage. Oxygen administration can improve short-term survival but appears to worsen respiratory failure, with no improvement in cardiac output or neuromuscular dysfunction. Oxygen should be used with caution after massive chlorine inhalation, and the need for early assisted ventilation should be assessed in victims.

Cortical Substrate of Supraspinal Fatigue following Exhaustive Aerobic Exercise Localizes to a Large Cluster in the Anterior Premotor Cortex.

Strenuous exercise leads to a progressive reduction in the performance of voluntary physical exercise. This is due to a process described as fatigue and is defined as the failure to maintain the required or expected power output. While some of this is muscular in origin, there are data suggestive of how fatigue is modulated by cortical signals, leading to a concept of central fatigue. The previously reported fatigue-induced changes in cortical activity may have been due to blood oxygen-dependent (BOLD) signal drift and/or neural habituation alone. We implemented a functional magnetic resonance imaging paradigm to effectively isolate brain areas responsible for central (supraspinal) fatigue following exercise. Our data identify a large cluster that includes dominant the anterior ventral premotor cortex (aPMv), the insula and postcentral gyrus as critical nodes in the brain network where supraspinal fatigue might have their functional neural imprints. Findings here show that activity in the ipsilateral aPMv and the adjacent areas in the premotor cortex correlates with both localized fatigue (fatigue specific hand grip contraction), and generalized full body exhaustive fatigue. In addition, from a methodological standpoint, we have also shown that the effects of BOLD signal drift can be modeled and removed to arrive at specific brain activity patterns in our experiments. Once the loci of central fatigue are isolated in this way, treatments aimed at modulating activity in these premotor areas may reduce exercise-induced fatigue and perhaps also benefit various clinical conditions in which fatigue is a major symptom.

Self-reported hypoglycemia in insulin-treated patients with diabetes: Results from an international survey on 7289 patients from nine countries.

AIMS: Hypoglycemia constitutes a significant barrier to achieving glycemic control with insulin in both type 1 and type 2 diabetes. Historically, it has been difficult to accurately verify the rates of hypoglycemia within a clinical setting and there is a need for high-quality, real-world data to ascertain the true rates of hypoglycemia in clinical practice. The global Hypoglycemia Assessment Tool (HAT) study was designed to assess the global incidence of hypoglycemia in patients with insulin-treated diabetes, and the results have indicated that the overall incidence of hypoglycemia is high, with large variations between geographical regions. METHODS: The International Operations HAT (IO HAT) study retrospectively and prospectively assessed the incidence of hypoglycemia in patients with insulin-treated diabetes in Bangladesh, Colombia, Egypt, Indonesia, Philippines, Singapore, South Africa, Turkey, and United Arab Emirates. RESULTS: During the prospective period, hypoglycemic events were reported by 97.4% of patients with type 1 diabetes and 95.3% of those with type 2 diabetes, with an estimated rate of 6.86 events per patient per month (PPPM) for patients with type 1 diabetes and 2.37 events PPPM for patients with type 2 diabetes. CONCLUSIONS: These results represent the first patient-reported dataset on hypoglycemia in the participating countries and confirm that hypoglycemia is under-reported and more widespread than previously believed. Although the incidence of hypoglycemia was variable among patients on different treatment regimens, there were substantial impacts on both productivity and healthcare utilization following an episode of hypoglycemia. This trial is registered at clinicaltrials.gov: NCT02306681.

Fatty acid amide hydrolase (FAAH) blockade ameliorates experimental colitis by altering microRNA expression and suppressing inflammation.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), which is thought to result from immune-mediated inflammatory disorders, leads to high morbidity and health care cost. Fatty acid amide hydrolase (FAAH) is an enzyme crucially involved in the modulation of intestinal physiology through anandamide (AEA) and other endocannabinoids. Here we examined the effects of an FAAH inhibitor (FAAH-II), on dextran sodium sulphate (DSS)-induced experimental colitis in mice. Treatments with FAAH-II improved overall clinical scores by reversing weight loss and colitis-associated pathogenesis. The frequencies of activated CD4+ T cells in spleens, mesenteric lymph nodes (MLNs), Peyer's patches (PPs), and colon lamina propiria (LP) were reduced by FAAH inhibition. Similarly, the frequencies of macrophages, neutrophils, natural killer (NK), and NKT cells in the PPs and LP of mice with colitis declined after FAAH blockade, as did concentrations of systemic and colon inflammatory cytokines. Microarray analysis showed that 26 miRNAs from MLNs and 217 from PPs had a 1.5-fold greater difference in expression after FAAH inhibition. Among them, 8 miRNAs were determined by reverse-transcription polymerase chain reaction (RT-PCR) analysis to have anti-inflammatory properties. Pathway analysis demonstrated that differentially regulated miRNAs target mRNA associated with inflammation. Thus, FAAH-II ameliorates experimental colitis by reducing not only the number of activated T cells but also the frequency of macrophages, neutrophils, and NK/NKT cell, as well as inflammatory miRNAs and cytokine at effector sites in the colon. These studies demonstrate for the first time that FAAH-II inhibitor may suppress colitis through regulation of pro-inflammatory miRNAs expression.

Sexual Health Knowledge, Self-Efficacy and Behavioral Intentions Following a Health Fair for Adolescents.

High rates of human immunodeficiency virus (HIV) exist among urban African American youth. There is a need to provide HIV information to youth prior to the onset of sexual activity. The Stomping Out HIV intervention combines a health fair and step show to increase awareness and healthy behaviors among this population. Questionnaires were administered to youth and parents before and after Stomping Out, and focused on health knowledge, satisfaction with Stomping Out, intended behavior changes and self-efficacy to make healthier choices related to HIV and STI prevention. Youth and adults reported increased knowledge and self-efficacy after Stomping Out. These findings suggest that health initiatives focusing on sociocultural issues can greatly impact adults and youth.